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EC number: 232-178-2 | CAS number: 7789-60-8
- Life Cycle description
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- Endpoint summary
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- Ecotoxicological Summary
- Aquatic toxicity
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- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
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- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
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Endpoint summary
Administrative data
Description of key information
Repeated dose toxicity: Inhalation
5 days repeated dose inhalation toxicity study was performed to determine the toxic nature of Phosphorus tribromide upon repeated exposure by inhalation route. Males CDF®[F-344]/CrIBR rats were treated at dose levels of 0.05, 0.1 or 0.5 mg/L test chemical in vapout form for 4h/days for 5 days by the nose only route of exposure. Mean ± SD exposure concentrations were 0.06 ± 0.01,0.16 ± 0.03, and 0.51 ± 0.08 mg/L respectively. The doses were selected considering the results of acute inhalation toxicity test. Exposures were performed using Cannon chambers. The animals were observed for mortlaity and clinical signs, changes in body weight, hematological and clinical chemistry parameters and gross and histopathology observations were made. The animals did not show any signs of toxic stress or mortality during the 5 days observation period. Mean body weights decreased in 0.05, 0.1 and 0.5 mg/L test groups and were significantly different in the 0.5 mg/L group when compared to control on Study Days 3 and 4. Statistically significant differences between control and PBr3- exposed animals were observed in several mean values of serum chemistry and hematologic parameters. Increases in serum chloride values were attributable to interference with the presence of serum bromide. Increased values in calcium and potassium were noted in the 0.5 mg/L group. Decreased values when compared to control were observed in alkaline phosphatase and creatine kinase in the 0.5 mg/L group; ALT values in the 0.1 mg/L and 0.5 mg/L groups. Additional statistically significant differences in mean values of hematologic parameters were sporadic and were not considered biologically important. No statistically significant differences in the organ weight were noted in the test group as compared to control. Absolute organ weight means and mean organ weight to body weight ratios revealed no statistically significant differences compared to control animals. Irregular shaped and reddened nares were observed in 3 of 5 animals at 0.5 mg/L. No other gross pathology lessions were noted in the test group and control animals. Microscopic lesions were observed in the 0.5 mg/L group and in the anterior-most segment of the nasal passages. In this group, suppurative (acute) inflammation of the mucosa of the nasal passages occurred at a statistically higher incidence than control animals (p<0.05). Chronic ulceration of the epithelium of the external nares was observed in 3 of 5 animals. Minimal squamous metaplasia of the respiratory epithelium was observed in the trachea of one rat in the high concentration group. In the 0.1 mg/L PBr3 group, 1 of 5 rats had slight inflammation of the nasal mucosa (most anterior regions). There were no microscopic lesions in rats of the 0.06 mg/L and control groups. Based on the observations made, the No Observed Adverse Effect Concentration (NOAEC) for phosphorus tribromide in a 5 days exposure period is considered to be 0.05 mg/L air.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from NTRL report
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- 5 days repeated dose inhalation toxicity study was performed to determine the toxic nature of Phosphorus tribromide upon repeated exposure by inhalation route.
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material: Phosphorus tribromide
- Molecular formula: Br3P
- Molecular weight: 270.686 g/mol
- Substance type: Inorganic
- Physical state: Colourless to pale yellow liquid
- Purity: 99.99+ %
- Impurities (identity and concentrations): No data available - Species:
- rat
- Strain:
- Fischer 344
- Remarks:
- CDF®[F-344]/CrIBR
- Details on species / strain selection:
- No data
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: No data available
- Weight at study initiation: Males: 100-125g and Females- 75-100 g
- Fasting period before study: No fasting before study
- Housing: the animals (two per cage) were housed in laminar air flow rooms in clear plastic cages with hardwoodchip bedding
- Diet (e.g. ad libitum): Purina Certified Rodent Diet #5002 ad libitum except during the inhalation exposure period
- Water (e.g. ad libitum): Water ad libitum except during the inhalation exposure period and for 12 h prior to sacrifice for the 5-day study
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 25°C
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): light/dark cycle was set at 12-h intervals
IN-LIFE DATES: From: To: No data available - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Cannon chambers
- Method of holding animals in test chamber: Plexiglas restraining tubes with nose only chambers were used to hold the test animals
- Source and rate of air: Four Cannon nose-only inhalation chambers were supplied with dried laboratory air with a minimal air flow delivery rate of 500 mL/animal
- Method of conditioning air: No data
- System of generating particulates/aerosols: The required concentration of phosphorous tribromide was generated using Sage syringe pumps delivering the required mass of test material into the air supply for the Cannon-52 chambers.
- Temperature, humidity, pressure in air chamber: The temperature of the carrier air was monitored
- Air flow rate: 500 mL/min of dry (<3% RH) filtered house air with a minimum of 10 L/min used for each of the test groups
- Air change rate: No data available
- Method of particle size determination: No data available
- Treatment of exhaust air: A bypass and containment dump system was employed to allow for smooth initiation of exposures and for use as a safety measure in case of abnormal syringe pump operation. The containment areas were further isolated vfrom the general laboratory area through use of a separate exhaust line which vented the enclosures.
TEST ATMOSPHERE
- Brief description of analytical method used: A Bromide specific ion electrode permitted quantification of the test material concentration through analysis of the bromide ion absorbed in an ionic strength buffer (pH 4.0). In order to monitor the lower concentrations, the ratio of vapor sample to buffer had to be increased from 10:1 air/absorber to 20:1 and 40:1. This allowed operation in the linear portion of the response curve. Sixty-mL plastic syringes containing 5.0 mL buffer were used to quantify the 50 mL vapor samples and acted as the reaction vessel for the absorption of PBr3. Multiple absorption samples were required to analyze the lower chamber concentrations.
- Samples taken from breathing zone: No data available
VEHICLE (if applicable)
- Justification for use and choice of vehicle: Air
- Composition of vehicle: No data available
- Type and concentration of dispersant aid (if powder): No data available
- Concentration of test material in vehicle: 0, 0.05, 0.1, and 0.5 mg/L (Mean ± SD exposuer concentrations are 0.06 ± 0.01,0.16 ± 0.03, and 0.51 ± 0.08 mg/L)
- Lot/batch no. of vehicle (if required): No data available
- Purity of vehicle: No data available - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- A Bromide specific ion electrode permitted quantification of the test material concentration through analysis of the bromide ion absorbed in an ionic strength buffer (pH 4.0). In order to monitor the lower concentrations, the ratio of vapor sample to buffer had to be increased from 10:1 air/absorber to 20:1 and 40:1. This allowed operation in the linear portion of the response curve. Sixty-mL plastic syringes containing 5.0 mL buffer were used to quantify the 50 mL vapor samples and acted as the reaction vessel for the absorption of PBr3. Multiple absorption samples were required to analyze the lower chamber concentrations.
- Duration of treatment / exposure:
- Duration of treatment: 1 week
Duration of exposure: 5 days - Frequency of treatment:
- 4 h/day for 5 consecutive days
- Remarks:
- 0, 0.05, 0.1, and 0.5 mg/L (Mean ± SD exposuer concentrations are 0.06 ± 0.01,0.16 ± 0.03, and 0.51 ± 0.08 mg/L)
- No. of animals per sex per dose:
- Total: 20
0 mg/L: 5 males
0.05 mg/L: 5 males
0.1 mg/L: 5 males
0.5 mg/L: 5 males - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The highest concentration of PBr3 was determined considering the results of the acute inhalation toxicity test
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data - Positive control:
- No data
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations checked in table [No.?] were included. Animals were observed for visible signs of toxicity
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: terminal body weight was recorded prior to necrospy
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at necrospy
- Anaesthetic used for blood collection: No data
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. WBC, RBC, HGB, HCT, MCV, MCH, MCHC, Platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at necropsy
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. BUN, creatinine, chloride, calcium, P, Total protein, AST, ALT, Alkaline phosphatase, glucose, Na, Mg, K, Cholesterol, triglycerides, Total bilirubin, ALB/GLOB, CO2, Uric acid, albumin, creatine, kinase and LDH
URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available
NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
OTHER: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, wet tissue weights were determined for heart, kidneys, testes, liver, lungs, brain, spleen, thymus, and adrenal glands at necrospy. Gross pathology was performed on each rat
HISTOPATHOLOGY: Yes, The upper respiratory tract and gross lesions were taken for histopathologic examination. - Other examinations:
- No data
- Statistics:
- Body weights were analyzed using the repeated mUltivariate analysis of variance with Scheffe pairwise comparisons. Hematology, clinical chemistry, and organ weights were analyzed using a two-factorial analysis of variance with multivariate comparisons. Histopathology data were analyzed through use of the Fischer Exact Test, or, if not valid, Yates' Corrected Chi-square was used.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Clinical signs and mortality
Mortality: No mortality was observed during 5 day exposure period
Clinical signs: No signs of toxic stress were noted dring the 5 day exposure period.
Body weight and weight gain: Mean body weights decreased in 0.05, 0.1 and 0.5 mg/L test groups and were significantly different in the 0.5 mg/L group when compared to control on Study Days 3 and 4.
Food consumption and compound intake: No data available
Food efficiency: No data available
Water consumption and compound intake: No data available
Opthalmoscopic examination: No data available
Haematology: Statistically significant differences between control and PBr3- exposed animals were observed in several mean values hematologic parameters including basophils and monocytes at 0.05 mg/L. Additional statistically significant differences in mean values of hematologic parameters were sporadic and were not considered biologically important.
Clinical chemistry: Statistically significant differences between control and PBr3- exposed animals were observed in several mean values of serum chemistry and hematologic parameters. Increases in serum chloride values were attributable to interference with the presence of serum bromide. Increased values in calcium and potassium were noted in the 0.5 mg/L group. Decreased values when compared to control were observed in alkaline phosphatase and creatine kinase in the 0.5 mg/L group; ALT values in the 0.1 mg/L and 0.5 mg/L groups. Additional statistically significant differences in mean values of hematologic parameters were sporadic and were not considered biologically important.
Urinanalysis: No data available
Neurobehaviour: No data available
Organ weights: No statistically significant differences in the organ weight were noted in the test group as compared to control. Absolute organ weight means and mean organ weight to body weight ratios revealed no statistically significant differences compared to control animals.
Gross pathology: Irregular shaped and reddened nares were observed in 3 of 5 animals at 0.5 mg/L. No other gross pathology lessions were noted in the test group and control animals.
Histopathology: Microscopic lesions were observed in the 0.5 mg/L group and in the anterior-most segment of the nasal passages. In this group, suppurative (acute) inflammation of the mucosa of the nasal passages occurred at a statistically higher incidence than control animals (p<0.05). Chronic ulceration of the epithelium of the external nares was observed in 3 of 5 animals. Minimal squamous metaplasia of the respiratory epithelium was observed in the trachea of one rat in the high concentration group. In the 0.1 mg/L PBr3 group, 1 of 5 rats had slight inflammation of the nasal mucosa (most anterior regions). There were no microscopic lesions in rats of the 0.05 mg/L and control groups. - Dose descriptor:
- NOAEC
- Effect level:
- 0.05 mg/L air
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No significant and adverse effect were noted at the mentioned dose level
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse Effect Concentration (NOAEC) for phosphorus tribromide in a 5 days exposure period is considered to be 0.05 mg/L air.
- Executive summary:
5 days repeated dose inhalation toxicity study was performed to determine the toxic nature of Phosphorus tribromide upon repeated exposure by inhalation route. Males CDF®[F-344]/CrIBR rats were treated at dose levels of 0.05, 0.1 or 0.5 mg/L test chemical in vapout form for 4h/days for 5 days by the nose only route of exposure. Mean ± SD exposure concentrations were 0.06 ± 0.01,0.16 ± 0.03, and 0.51 ± 0.08 mg/L respectively. The doses were selected considering the results of acute inhalation toxicity test. Exposures were performed using Cannon chambers. The animals were observed for mortlaity and clinical signs, changes in body weight, hematological and clinical chemistry parameters and gross and histopathology observations were made. The animals did not show any signs of toxic stress or mortality during the 5 days observation period. Mean body weights decreased in 0.05, 0.1 and 0.5 mg/L test groups and were significantly different in the 0.5 mg/L group when compared to control on Study Days 3 and 4. Statistically significant differences between control and PBr3- exposed animals were observed in several mean values of serum chemistry and hematologic parameters. Increases in serum chloride values were attributable to interference with the presence of serum bromide. Increased values in calcium and potassium were noted in the 0.5 mg/L group. Decreased values when compared to control were observed in alkaline phosphatase and creatine kinase in the 0.5 mg/L group; ALT values in the 0.1 mg/L and 0.5 mg/L groups. Additional statistically significant differences in mean values of hematologic parameters were sporadic and were not considered biologically important. No statistically significant differences in the organ weight were noted in the test group as compared to control. Absolute organ weight means and mean organ weight to body weight ratios revealed no statistically significant differences compared to control animals. Irregular shaped and reddened nares were observed in 3 of 5 animals at 0.5 mg/L. No other gross pathology lessions were noted in the test group and control animals. Microscopic lesions were observed in the 0.5 mg/L group and in the anterior-most segment of the nasal passages. In this group, suppurative (acute) inflammation of the mucosa of the nasal passages occurred at a statistically higher incidence than control animals (p<0.05). Chronic ulceration of the epithelium of the external nares was observed in 3 of 5 animals. Minimal squamous metaplasia of the respiratory epithelium was observed in the trachea of one rat in the high concentration group. In the 0.1 mg/L PBr3 group, 1 of 5 rats had slight inflammation of the nasal mucosa (most anterior regions). There were no microscopic lesions in rats of the 0.06 mg/L and control groups. Based on the observations made, the No Observed Adverse Effect Concentration (NOAEC) for phosphorus tribromide in a 5 days exposure period is considered to be 0.05 mg/L air.
Reference
TABLE 1. Mean body weight of male F-344 rats during five-day, nose-only inhalation exposure to phosphorus tribromide or air
Day |
Control |
0.05 mg/L |
0.1 mg/L |
0.5 mg/L |
0 |
258.2 ± 8.0 |
259.0 ± 10.4 |
255.6 ± 12.5 |
258.8 ± 10.7 |
1 |
250.4 ±7.9 |
251.0 ± 10.5 |
245.3 ± 13.8 |
247.7 ± 12.6 |
2 |
245.4 ± 8.3 |
245.9 ± 9.4 |
241.6 ± 12.9 |
239.9 ± 10.2 |
3 |
242.7 ± 9.0 |
242.9 ± 9.8 |
237.3 ± 13.1 |
234.7 ± 9.9b |
4 |
241.2 ± 9.0 |
240.5 ± 10.5 |
236.3 ± 12.0 |
229.0 ± 8.5b |
5 |
225.7 ± 8.6 |
225.2 ± 8.6 |
220.6 ± 10.6 |
214.4 ± 7.9 |
a Mean ± SD, N=5.
b Significantly different from control at p<0.01.
TABLE 2. Mean Values· Of Serum Chemistry Parameters For Male F-344 Rats After Five-Day, Nose-Only Inhalation Exposure To Phosphorus Tribromide
Parameter |
Control |
0.05 mg/L |
0.1 mg/L |
0.5 mg/L |
BUN (mg/dL) |
15.8 ± 0.4 |
13.4 ± 1.3b |
15.4 ± 1.1 |
16.6 ± 1.5 |
Chloride (mmol/L) |
95.0 ± 1.2 |
99.2 ± 3.5 |
106.0 ± 1.4c |
130.4 ± 3.1 c |
Calcium (mmoIlL) |
11.6 ± 0.3 |
11.4 ± 0.5 |
11.9 ± 0.4 |
12.4 ± 0.2b |
ALT (IU/L) |
59.8 ± 5.1 |
55.0 ±6.4 |
47.4 ± 6.1 b |
38.4 ± 3.7c |
Alkaline Phosphatase (lU/L) |
151.0 ± 2.9 |
147.2 ± 12.1 |
139.0 ± 7.0 |
132.6 ± 8.4b |
Potassium (mmol/L) |
4.8 ± 0.3 |
4.8 ± 0.1 |
4.7 ± 0.1 |
5.4 ± 0.2c |
Creatine Kinase (lUlL) |
69.0 ±6.0 |
75.0 ± 16.3 |
59.8 ± 14.4 |
45.6 ± 10.7 b |
a Mean ± SO, N =5.
b Significantly different from control at p<0.05.
c Significantly different from control at p<0.01.
TABLE 3. Blood Hematology Values For Male F-344 Rats After Five-Day, Nose-Only Inhalation Exposure To Phosphorus Tribromide
Parameter |
Control |
0.05 mg/L |
0.1 mg/L |
0.5 mg/L |
Monocytes %) |
6.3 ± 0.8 |
1.2±2.1b |
4.4 ± 3.2 |
6.3 ±3.5 |
Basophils (%) |
0.4 ± 0.2 |
<0.1 ± <0.1 b |
0.2 ± 0.2 |
0.3 ± 0.2 |
a Mean ± SD, N = 5.
b Significantly different from control at p<0.05.
TABLE 4. Organ Weights and Organ-To-Bodyweight Ratios Of Male F-344 Rats After Five-Day, Nose-Only Inhalation Exposure To Phosphorus Tribromide
Organ |
Control |
0.05 mg/L |
0.1 mg/L |
0.5 mg/L |
Body Wt |
226 ± 8.6 |
225 ± 8.6 |
221 ± 10.6 |
214 ± 7.9 |
Liver |
7.12 ± 0.72 |
6.88 ± 0.57 |
6.65 ± 0.37 |
6.47 ± 0.56 |
Kidneys |
1.77 ± 0.08 |
1.76 ± 0.08 |
1.52 ± 0.41 |
1.68 ± 0.08 |
Testes |
2.84 ± 0.13 |
2.78 ± 0.09 |
2.53 ± 0.46 |
2.65 ± 0.12 |
Brain |
1.79 ± <0.01 |
1.79 ± 0.04 |
1.78 ± 0.01 |
1.74 ± 0.06 |
Adrenals |
0.04 ± 0.02 |
0.05 ± 0.01 |
0.05 ± 0.01 |
0.05 ± 0.01 |
Lungs |
1.45 ± 0.14 |
1.34 ± 0.10 |
1.46 ± 0.07 |
1.09 ± 0.61 |
Thymus |
0.25 ± 0.04 |
0.22 ± 0.03 |
0.20 ± 0.03 |
0.19 ± 0.02 |
Heart |
0.79 ± 0.04 |
0.81 ± 0.05 |
0.81 ± 0.02 |
0.82 ± 0.06 |
a Mean ± SO, N=5.
b Organ weight/body weight x 100.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 0.05 mg/m³
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is from K4 NTRL report
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity: Inhalation
Data available for the target chemical was reviewed to determine the toxic nature of Phosphorus tribromide upon repeated exposure by inhalation route. The studies are as mentioned below:
5 days repeated dose inhalation toxicity study was performed by Wolf et al ( ManTech / GEO-CENTERS Joint Venture,Armstrong Laboratory, Occupational and Environmental Health Directorate Toxicology Division, Human Systems Center Air Force Materiel Command,WrilZht-Patterson., 1997) to determine the toxic nature of Phosphorus tribromide upon repeated exposure by inhalation route. Males CDF®[F-344]/CrIBR rats were treated at dose levels of 0.05, 0.1 or 0.5 mg/L test chemical in vapout form for 4h/days for 5 days by the nose only route of exposure. Mean ± SD exposure concentrations were 0.06 ± 0.01,0.16 ± 0.03, and 0.51 ± 0.08 mg/L respectively. The doses were selected considering the results of acute inhalation toxicity test. Exposures were performed using Cannon chambers. The animals were observed for mortlaity and clinical signs, changes in body weight, hematological and clinical chemistry parameters and gross and histopathology observations were made. The animals did not show any signs of toxic stress or mortality during the 5 days observation period. Mean body weights decreased in 0.05, 0.1 and 0.5 mg/L test groups and were significantly different in the 0.5 mg/L group when compared to control on Study Days 3 and 4. Statistically significant differences between control and PBr3- exposed animals were observed in several mean values of serum chemistry and hematologic parameters. Increases in serum chloride values were attributable to interference with the presence of serum bromide. Increased values in calcium and potassium were noted in the 0.5 mg/L group. Decreased values when compared to control were observed in alkaline phosphatase and creatine kinase in the 0.5 mg/L group; ALT values in the 0.1 mg/L and 0.5 mg/L groups. Additional statistically significant differences in mean values of hematologic parameters were sporadic and were not considered biologically important. No statistically significant differences in the organ weight were noted in the test group as compared to control. Absolute organ weight means and mean organ weight to body weight ratios revealed no statistically significant differences compared to control animals. Irregular shaped and reddened nares were observed in 3 of 5 animals at 0.5 mg/L. No other gross pathology lessions were noted in the test group and control animals. Microscopic lesions were observed in the 0.5 mg/L group and in the anterior-most segment of the nasal passages. In this group, suppurative (acute) inflammation of the mucosa of the nasal passages occurred at a statistically higher incidence than control animals (p<0.05). Chronic ulceration of the epithelium of the external nares was observed in 3 of 5 animals. Minimal squamous metaplasia of the respiratory epithelium was observed in the trachea of one rat in the high concentration group. In the 0.1 mg/L PBr3 group, 1 of 5 rats had slight inflammation of the nasal mucosa (most anterior regions). There were no microscopic lesions in rats of the 0.06 mg/L and control groups. Based on the observations made, the No Observed Adverse Effect Concentration (NOAEC) for phosphorus tribromide in a 5 days exposure period is considered to be 0.05 mg/L air.
In the same study by Wolfe et al (1997), Subchronic repeated dose inhalation toxicity study was also performed to determine the toxic nature of Phosphorus tribromide upon repeated exposure by inhalation route. Males CDF®[F-344]/CrIBR rats were treated at dose levels of 0.03, 0.1 or 0.3 mg/L test chemical in vapour form for 4h/days excluding weekends for 28 days by the nose only route of exposure. Mean ± SD exposure concentrations were 0.30 ± 0.03, 0.11 ± 0.01, and 0.034 ± 0.004 mg/L respectively. The doses were selected considering the results of acute inhalation toxicity test. Exposures were performed using four Cannon chambers. The animals were observed for mortlaity and clinical signs, changes in body weight, hematological and clinical chemistry parameters and gross and histopathology observations were made. The animals did not show any signs of toxic stress or mortality during the observation period. Mean body weights for male and female rats in the control and PBr3 exposure groups were similar. Slight increases in mean corpuscular volume, monocytes, and eosinophils were observed in the high concentration exposed rats. A concentration-related decrease in platelets was observed in rats of the 0.3, 0.1, and 0.03 mg/L groups. Additional statistically significant differences in mean values of hematologic parameters were sporadic and were not considered biologically significant. Mean values of several serum chemistry and hematologic parameters were statistically significantly different in PBr3 animals compared to those of the control group. Increases in serum chloride concentrations in rats of the 0.3 and 0.1 mg/L groups were observed and attributable to interference with the presence of serum bromide. A small increase in chloride values and a small decrease in ALT levels were observed in rats exposed to 0.3 mg/L PBr3. Though not concentration-related, an 11-26 % decrease in triglycerides was observed in all groups of rats exposed to PBr3. No treatment related chenges in absolute and relative organ weights were noted. No treatment-related gross lesions were observed in the test group animals. Tissues from rats of the 0.3 mg/L PBr3 and air-only control groups were examined microscopically. The only treatment-related finding was the presence of exudate or evidence of mild inflammation of the anterior nasal passages in 3 of 10 male rats and 1 of 10 female rats. This finding was not statistically significant compared to the control group values. Based on the observations made, the No Observed Adverse Effect Concentration (NOAEC) for phosphorus tribromide in a 28 days exposure period is considered to be 0.1 mg/L air when exposed to male and female CDF®[F-344]/CrIBR for 28 days.
Based on the data available for the target chemical, phosphorus tribromide does not exhibit toxic nature upon repeated exposure by inhalation route. Hence the test chemical is not likely to classify as a toxicant upon repeated exposure by inhalation route.
Justification for classification or non-classification
Based on the data available for the target chemical, phosphorus tribromide does not exhibit toxic nature upon repeated exposure by inhalation route. Hence the test chemical is not likely to classify as a toxicant upon repeated exposure by inhalation route.
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